Plasmodium falciparum dipeptidyl aminopeptidase 3 activity is important for efficient erythrocyte invasion by the malaria parasite
Rattachement africain : gb, nl, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Parasite egress from infected erythrocytes and invasion of new red blood cells are essential processes for the exponential asexual replication of the malaria parasite. These two tightly coordinated events take place in less than a minute and are in part regulated and mediated by proteases. Dipeptidyl aminopeptidases (DPAPs) are papain-fold cysteine proteases that cleave dipeptides from the N-terminus of protein substrates. DPAP3 was previously suggested to play an essential role in parasite egress. However, little is known about its enzymatic activity, intracellular localization, or biological function. In this study, we recombinantly expressed DPAP3 and demonstrate that it has indeed dipeptidyl aminopeptidase activity, but contrary to previously studied DPAPs, removal of its internal prodomain is not required for activation. By combining super resolution microscopy, time-lapse fluorescence microscopy, and immunoelectron microscopy, we show that Plasmodium falciparum DPAP3 localizes to apical organelles that are closely associated with the neck of the rhoptries, and from which DPAP3 is secreted immediately before parasite egress. Using a conditional knockout approach coupled to complementation studies with wild type or mutant DPAP3, we show that DPAP3 activity is important for parasite proliferation and critical for efficient red blood cell invasion. We also demonstrate that DPAP3 does not play a role in parasite egress, and that the block in egress phenotype previously reported for DPAP3 inhibitors is due to off target or toxicity effects. Finally, using a flow cytometry assay to differentiate intracellular parasites from extracellular parasites attached to the erythrocyte surface, we show that DPAP3 is involved in the initial attachment of parasites to the red blood cell surface. Overall, this study establishes the presence of a DPAP3-dependent invasion pathway in malaria parasites.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Plasmodium falciparum dipeptidyl aminopeptidase 3 activity is important for efficient erythrocyte invasion by the malaria parasite
- Date Crossref
- 16/05/2018
- Éditeur
- Public Library of Science (PLoS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
The Francis Crick Institute pays non établi dans la noticeStructure de recherche
-
Radboud University Nijmegen pays non établi dans la noticeUniversité ou école supérieure
-
Radboud University Medical Center Department of Medical Microbiology pays non établi dans la noticeOrganisme public
-
University of Manchester pays non établi dans la noticeUniversité ou école supérieure
-
Stanford Medicine pays non établi dans la noticeÉtablissement de santé
-
Washington University in St. Louis pays non établi dans la noticeUniversité ou école supérieure
-
Chemical Biology Approaches to Malaria Laboratory pays non établi dans la noticeStructure de recherche
-
Faculty of Life Sciences pays non établi dans la noticeUniversité ou école supérieure
-
Stanford School of Medicine Department of Genetics pays non établi dans la noticeUniversité ou école supérieure
-
Washington University School of Medicine Departments of Molecular Microbiology and Medicine pays non établi dans la noticeUniversité ou école supérieure
The Francis Crick Institute, Radboud University Nijmegen et Department of Medical Microbiology — Radboud University Medical Center, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.